Inflammation
lecture 4
Dr Heyam Awad
FRCPath
Chemical mediators of inflammation
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VASOACTIVE AMINES
AA METABOLITES
PAF
CYTOKINES
REACTIVE OXYGEN SPECIES
REACTIVE NITROGEN SPECIES
LYSOSOMAL ENZYMES
NEUROPEPTIDE
COMPLEMENT SYSTEM
KININ SYSTEM
Platelet activating factor
• Generated from membrane phospholipids by
phospholipase A2.
• Neutrophils, monocytes, basophils, platelet,
endothelial cells and other cells.
• Potent broncho-constrictor.
• Potent vasodilator.
• Stimulates synthesis of other mediators.
cytokines
• Polypeptides.
MAJOR CYTOKINES:
• TNF,
• IL 1,
• IL 6
• CHEMOKINES.
TNF and IL 1
• Main role: endothelial activation.
Stimulate expression of adhesion
molecules on endothelial cells.
• Increase production of other cytokines and AA
metabolites.
TNF and IL1
Cause systematic effects:
• Fever
• Lethargy
• Decreased blood pressure
chemokines
• Small protein that are chemoattractant to
WBCs.
• Most important: IL8.
• They also activate WBCs… e: g by increasing
affinity of leukocyte integrins to their ligands
on endothelium.
neuropeptide
• E: g substance P.
• Transmit pain signals.
• Regulate vessel tone.
Nitric oxide
• Short lived soluble free radical gas.
• Synthesized de novo from arginine by nitric
oxide synthase (NOS)
NOS
• Type 1, neuronal.. No role in inflammation.
• Type 2.. inducible, macrophages and
endothelial cells
• Type 3 in endothelial cells.
Effects of NO
• Microbicidal
• Vasodilator
• Reduced leukocyte recruitment
Plasma derived mediators
• Complement system
• Coagulation system
• Kinin system
complement
Coagulation and kinin
Systemic effects of inflammation
• = acute phase reaction:
• Most importan mediators: TNF, IL 1 , IL 6.
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Fever,
elevated acute phase proteins,
leukocytosis.
Increased heart rate and blood pressure.
fever
• Pyrogens are substances that stimulate
prostaglandin synthesis in the hypothalamus.
• PG in hypothalamus.. Stimulate production of
neurotransmitters which increase
temperature.
• Internal (IL 1 and TNF) and external pyrogens(
bacterial lipopolysaccharides).
Elevated acute phase proteins
• Acute phase proteins: plasma proteins
synthesized in the liver due to influence of
cytokines, mainly IL 6.
• Most important: C reactive protein (CRP),
fibrinogen and serum amyloid A (SAA)
• CRP and SAA act as opsonins.
• Fibrinogen binds to RBCs so they form
aggregates that sediment more rapidly at unit
gravity than individual erythrocytes.
ESR
• Erythrocyte sedimentation rate.
• Measures the sedimentation of RBCs .
• Good measure of inflammation.
leukocytosis
• WBCs 15-20 000 cells/ml in inflammation.
• Rarely reaches 40-100000 =leukemoid
reaction.
Other systemic manifestations
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Increased heart rate.
High blood pressure.
Decreased sweating.
Malaise
Anorexia.